Differential clot stabilising effects of rFVIIa and rFXIII-A2 in  whole blood from thrombocytopenic patients and  healthy volunteers.
The haemostatic effect of recombinant activated factor VII (rFVIIa;NovoSeven) in thrombocytopenic patients has been a matter of controversy. Haemostasis by rFVIIa occurs via FVIIa-mediated thrombin generation in a platelet-dependent manner and may therefore be suboptimal in patients without functional platelets. Under such conditions, a clot-stabilizing agent, such as factor XIII (FXIII), may supplement the effect ofrFVIIa and improve haemostasis. Recombinant factor XIII (rFXIII-A2) is produced as an A2 homodimer of the FXIII A subunit and is equivalent to cellular FXIII normally found in platelets. The combined effects of rFVIIa andrFXIII-A2 were evaluated in clot lysis assays using factor XIII-deficient plasma and by whole blood thrombelastography (TEG) analysis from normal donors and thrombocytopenic stem cell transplantation patients. Clotting time was shortened by rFVIIa (0.6-10 microg/ml). rFVIIa only modestly improved anti-fibrinolysis,whereas rFXIII-A2 (0-20 microg/ml) enhanced anti-fibrinolysis without effect on clotting time. TEG analysis showed rFVIIa shortened the clotting time, and enhanced clot development, maximal mechanical strength and resistance to fibrinolysis, whereas, rFXIII-A2 enhanced clot development,maximal mechanical strength and markedly enhanced resistance to fibrinolysis. These data illustrate that rFVIIa and rFXIII-A2 contribute to clot formation and stability by different mechanisms suggesting enhanced haemostatic efficacy by combining these agents.
Johansson
Pär I
PI
Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. per.johansson@rh.hosp.dk
Jacobsen
Niels
N
Viuff
Dorthe
D
Olsen
Eva H N
EH
Rojkjaer
Rasmus
R
Andersen
Søren
S
Petersen
Lars C
LC
Kjalke
Marianne
M
D001772:Blood Cell Count; D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015942:Factor VIIa / Q000494:pharmacology*; D026122:Factor XIIIa / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D011994:Recombinant Proteins / Q000494:pharmacology; D033581:Stem Cell Transplantation; D013916:Thrombelastography / Q000379:methods; D013921:Thrombocytopenia / Q000097:blood* / Q000628:therapy
D011994:Recombinant Proteins; C103587:recombinant FVIIa; D026122:Factor XIIIa; D015942:Factor VIIa